O trabalho tem o objetivo de estudar a tutela inibitória no processo do trabalho, especialmente no sentido da prevenção do assédio moral no ambiente de trabalho. A abordagem parte da perspectiva da proteção dos direitos fundamentais dos trabalhadores, principalmente em face do poder diretivo do empregador. Analisa a vinculação dos particulares às normas de direitos fundamentais e ressalta a importância da vinculação direta ou imediata do empregador às normas de direitos fundamentais, no âmbito da relação de emprego. Põe em relevo a função do processo do trabalho na perspectiva da tutela dos direitos fundamentais. Analisa as características do assédio moral praticado no ambiente de trabalho, sua classificação e suas consequências. Trata das modificações sociais que impuseram novas necessidades ao direito processual, especialmente ao direito processual do trabalho. Aborda a natureza e as características da tutela inibitória, como tutela judicial preventiva da conduta ilícita. Trata dos meios concretos de operar a tutela inibitória no processo do trabalho, com o objetivo de prevenir o assédio moral. Cuida de aspectos controversos da legitimidade para a ação inibitória, bem como de peculiaridades da causa de pedir e da prova. Analisa os requisitos da sentença e da coisa julgada na ação inibitória. Conclama à assunção da lógica da prevenção no direito processual. Realça a necessidade de uma atuação mais criativa e livre dos juízes trabalhistas. / The work aims to study the inhibitory injunction in the labor process, especially towards the prevention of bullying in the workplace. The approach starts from the perspective of protecting the fundamental rights of workers, particularly against the directive power of the employer. Analyzes linking the particular standards of fundamental rights and emphasizes the importance of direct or immediate employer to binding rules relating to fundamental rights within the employment relationship. It highlights the role of the procedural labor law from the perspective of the protection of fundamental rights. It analyzes the characteristics of bullying practiced in the workplace, their classification and environmental consequences. It analyzes the social changes that have imposed new requirements of procedural law, especially procedural labor law. It approaches the nature and characteristics of inhibitory injunction, like a judicial protection as a preventive of unlawful conduct. It analyzes the specific means to operate the inhibitory injunction in the labor process, with the goal of preventing bullying. It takes care of controversial aspects of legitimacy to the inhibitory action, as well as peculiarities of the cause of action and proofs. It analyzes the requirements of the sentence and the inhibitory action on res judicata. It urges the assumption of prevention logic in procedural law. It stresses the need for a more creative and free activity of labor judges.

Submitted by Edineia Teixeira (edineia.teixeira@unioeste.br) on 2018-03-05T14:21:12Z No. of bitstreams: 2 Juliete_Souza2017.pdf: 1034930 bytes, checksum: b1f11241cc86452c59ec27f91ef18252 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-03-05T14:21:12Z (GMT). No. of bitstreams: 2 Juliete_Souza2017.pdf: 1034930 bytes, checksum: b1f11241cc86452c59ec27f91ef18252 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-03-08 / The genus Zanthoxylum comprises species distributed throughout tropical regions and temperate regions mainly. The plants of this genus are of great ethnobotanical, phytochemical importance. Z. caribaeum species are popularly known as thorn-billed thorns, thorny thorns, black hawthorn, stinky mammals, and stalks, and require further studies on its biological potential. In this study, the chemical composition, antimicrobial, antioxidant and acaricidal activities from different vegetal extracts (aqueous, ethanol, methanol, hexane, acetonide, dichloromethane and ethyl acetate) and from this species essencial oil were investigated. It was also determined the chemical composition of the essential oil of Z. caribaeum leaves through gas chromatography coupled to mass spectrometry (CG/MS), the antimicrobial activity of the extracts and of the essential oil was determined by measuring the Minimal Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) using broth dilution technique against pathogenic microorganisms such as Salmonella enterica subspecies enterica serovar Typhimurium (ATCC 14028), Salmonella enterica subspecies enterica serovar Enteretidis (ATCC 13076), Escherichia coli (ATCC 25922), Klebsiella pneumoniae ATCC 13883), Proteus mirabilis (ATCC 25933), Pseudomonas aeruginosa (ATCC 27853), Staphylococcus aureus (ATCC 25923), Staphylococcus epidermidis (ATCC 12228), Enterococcus faecalis (ATCC 19433), Bacillus subtilis subspecies spizizenii (CCCD B005), yeast Candida albicans (ATCC 10231) and against different serotypes of Salmonella enterica, occuring isolated in the western region of Paraná, Brazil. It was also evaluated the antioxidant activity of the essential oil by the DPPH (2,2-diphenyl-1-picryl-hydrazyl) free radical capture method, as well as its repellent capacity against Dermanyssus gallinae (Panzer) (Acari: Dermanyssidae), using Y-olfactometer. In general, the GC/MS of the essential oil was dominated by terpenes, the major compounds being Germacrene-D, -Panasinsene, -Selinene, Varidiflorene and -Elemene. Regarding the antimicrobial activity, except for the aqueous extract, all the extracts showed antimicrobial activity, in addition, the essential oil was effective against all the Gram-positive and Gram-negative bacteria tested and some different serotypes of Salmonella enterica. In relation to the antioxidant activity, the essential oil presented high antioxidant capacity, besides a repellent action of 79% against the mite D. gallinae. Thus, it is concluded that the results contribute to the chemical and biological characterization of the species Z. caribaeum, being a promising source of secondary metabolites with biological activities. / O gênero Zanthoxylum compreende espécies distribuídas mundialmente, principalmente em regiões tropicais e regiões temperadas. As plantas deste gênero têm grande importância etnobotânica, fitoquímica e a espécie Z. caribaeum é conhecida popularmente por espinho-de-barrão, espinho cheiroso, espinheiro-preto, mamiqueira-fedorenta, pau-de-barrão e necessita de mais estudos a respeito de seu potencial biológico. Diante disto, esta espécie foi o objeto de estudo, na qual foi investigada a composição química e as atividades biológicas antimicrobiana, antioxidante e acaricida dos diferentes extratos vegetais (aquoso, etanolico, metanolico, hexanico, acetonico, diclorometanico e de acetato de etila) e do óleo essencial. Também foi determinada a composição química do óleo essencial das folhas de Z. caribaeum através de cromatografia gasosa acoplada a espectofometria de massas (CG/EM), a atividade antimicrobiana dos extratos e do óleo essencial foi realizada pela determinação da Concentração Inibitória Mínima (CIM) e Concentração Bactericida Mínima (CBM) utilizando a técnica de diluição em caldo frente microrganismos patogênicos como Salmonella enterica subespécie enterica sorovar Typhimurium (ATCC 14028), Salmonella entérica subespécie enterica sorovar Enteretidis (ATCC 13076), Escherichia coli (ATCC 25922), Klebsiella pneumoniae (ATCC 13883), Proteus mirabilis (ATCC 25933), Pseudomonas aeruginosa (ATCC 27853), Staphylococcus aureus (ATCC 25923), Staphylococcus epidermidis (ATCC 12228), Enterococcus faecalis (ATCC 19433), Bacillus subtilis subespécie spizizenii (CCCD B005), a levedura Candida albicans (ATCC 10231) e frente a diferentes sorotipos de Salmonella enterica, de maior ocorrência e isoladas na região oeste do Paraná, Brasil. Avaliou-se também a atividade antioxidante do óleo essencial pelo método de captura de radicais livres DPPH (2,2difenil-1-picril-hidrazil), bem como, a sua capacidade repelente ao ácaro Dermanyssus gallinae (Panzer) (Acari: Dermanyssidae) pela utilização de olfatômetro em Y. De maneira geral, a CG/EM do óleo essencial verificou-se o predomínio de terpenos, sendo os compostos majoritários o Germacreno-D, -Panasinseno, -Selineno, Varidifloreno e -Elemeno. Em relação a atividade antimicrobiana, com exceção do extrato aquoso, todos os extratos vegetais apresentaram atividade antimicrobiana, além disto, o óleo essencial foi efetivo frente a todas as bactérias Gram-positivas e Gram-negativas testadas e alguns diferentes sorotipos de Salmonella enterica. Em relação a atividade antioxidante, o óleo essencial apresentou elevada capacidade antioxidante, além de ação repelente de 79% frente ao ácaro D. gallinae. Desta forma, conclui-se que os resultados contribuem para a caracterização química e biológica da espécie Z. caribaeum, sendo uma fonte promissora de metabolitos secundários com atividades biológicas.

Orientador: Patricia da Silva Melo, Priscyla Daniely Marcato / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Aplicadas / Made available in DSpace on 2018-08-26T08:22:25Z (GMT). No. of bitstreams: 1 Silva_JulianadeCassia_M.pdf: 2326263 bytes, checksum: 5774dc06c3b8cd0a38cfb05b3dbd8247 (MD5) Previous issue date: 2014 / Resumo: Com o objetivo de entender melhor a toxicidade das nanopartículas de prata biogênicas, estas foram preparadas utilizando a rota biotecnológica e extracelular com o fungo Fusarium oxysporum. As nanopartículas de prata biogênicas foram caracterizadas por microscopia eletrônica de transmissão (TEM) e absorbância na região do UV/Visível. O tamanho das nanopartículas foi determinado pela a técnica de análise de rastreamento de nanopartículas (NTA) utilizando o equipamento NanoSight, e por espectroscopia de correlação de fótons utilizando o equipamento ZetaSizer. O potencial zeta das partículas também foi avaliado no ZetaSizer. A atividade antimicrobiana, a citotoxicidade e os mecanismos de ação das nanopartículas de prata biogênicas em células V79 também foram investigados. A produção de nanopartículas de prata foi evidenciada pela presença da banda de absorção de plasma ('lâmbda' = 450 nm) e por TEM sendo observadas partículas esféricas com o tamanho de 15-22 nm. A atividade antibacteriana e antifúngica das nanopartículas de prata foi avaliada contra Staphylococcus aureus (MIC 1,47 µg mL-1), Salmonella typhymurium (MIC 0,36 µg mL-1), Escherichia coli (MIC 0,73 µg mL-1), Aspergillus niger (MIC 5,90 µg mL-1) e Trichophytum rubrum (MIC 2,95 µg mL-1). Além disso, a atividade bactericida das nanopartículas de prata foi diminuída na presença de glutationa reduzida, indicando que a eficácia antimicrobiana está provavelmente relacionada com a indução de estresse oxidativo. As nanopartículas de prata exibiram citotoxicidade dose dependente em células V79. Na concentração de 8,49 µg mL-1 as nanopartículas de prata promoveram 51% de morte celular avaliada pela redução do MTT e 37 % em ensaios de DNA. A presença de glutationa (307,3 µg mL-1) aumentou em 17 % a viabilidade celular, atingindo 66% de células viáveis no ensaio MTT e em 25 % no ensaio de DNA, atingindo 88% de células viáveis. Estes resultados podem indicar que os efeitos citotóxicos induzidos pelo tratamento de nanopartículas de prata biogênicas podem estar relacionadas com o estresse oxidativo. Este efeito pode ser muito importante na terapia de câncer e de antibióticos, e também para tratamento de doenças neurodegenerativas entre outras / Abstract: Aiming to understand better the toxicity of biogenic silver nanoparticles, these were prepared using biotechnological extracellular route and fungus Fusarium oxysporum. biogenic silver nanoparticles were then characterized by transmission electron microscopy and UV/Vis. Their size and zeta potential were determined using the nanoparticle tracking analysis software by Nanosight, photon correlation spectroscopy and zeta potential techniques. The antimicrobial activity, cytotoxicity and in vitro mechanism of biogenic silver nanoparticles action in V79 cells were also investigated. The biogenic silver nanoparticles production was evidenced by the presence of the plasmon absorption band ('lâmbda'= 450 nm) and spherical particles with the size of 15-22 nm were obtained. The biogenic silver nanoparticles antimicrobial and antifungal activity against Staphylococcus aureus (MIC 1.47 'mu'g mL-1), Salmonella typhymurium (MIC 0.36 'mu'g mL-1), Escherichia coli (MIC 0.73 ?g mL-1), Aspergillus niger (MIC 5.90 ?g mL-1) and Trichophytum rubrum (MIC 2.95 'mu'g mL-1) were measured. Furthermore, the bactericidal activity of AgNPbio decreased in the presence of reduced glutathione (GSH) indicating that antimicrobial effectiveness is probably related to oxidative stress induction. The biogenic silver nanoparticles exhibited cytotoxicty in some extent regarding V79 cells. At the concentration of 8.49 'mu'g mL-1 biogenic silver nanoparticles provoked 51% cell death in the MTT and 37% in DNA assays. The presence of glutathione (GSH, 307.3 ng mL-1) increased 17% cell viability on MTT and 25% on DNA assays. Obtained results may point out that the cytotoxic effects induced by biogenic silver nanoparticles treatment could be related to the oxidative stress. This effect can be very important in the cancer and antibiotic therapy and also for neurodegenerative and many other diseases treatments / Mestrado / Metabolismo e Biologia Molecular / Mestra em Ciências da Nutrição e do Esporte e Metabolismo

4 ABSTRACT Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Dimitrios Vagiannis Supervisor: RNDr. Jakub Hofman, Ph.D. Title of diploma thesis: Evaluation of antiproliferative effect of selected tyrosine kinase inhibitors in MDCKII cell lines Tyrosine kinases are important enzymes regulating crucial cellular processes including differentiation, proliferation, apoptosis, transcription, metabolism, and intercellular communication. Deregulation of these enzymes is the cause of various types of cancers. The blockade of their function by tyrosine kinase inhibitors (TKis) is considered a promising approach especially in antitumor pharmacotherapy. ATP-binding cassette (ABC) drug efflux transporters are a family of transmembrane proteins that pump a variety of structurally unrelated compounds out of the cell in an energy-dependent manner. They play an important role in pharmacokinetics (affect absorption, distribution, elimination) and, at the same time, can negatively influence efficacy of chemotherapy (participate in multidrug resistance phenomenon). In our research, we evaluated antiproliferative properties of four selected TKis, namely alectinib, brivanib, osimertinib and selumetinib, in MDCKII cell lines (parent one and those transduced with human...

Ma thèse est consacrée à l’étude des réseaux neuronaux spinaux impliqués dans la motricité chez l’Homme est comprend deux chapitres. Des travaux récents effectués sur la moelle épinière du rat ont mis en évidence qu’au cours du développement chez les mammifères, les synapses GABAergiques et glycinergiques sont tout d’abord excitatrices avant de devenir inhibitrices et qu’une section de la moelle épinière ne permet pas cette transformation. Cette transition développementale semble due à l’action d’un transporteur transmembranaire (KCC2) au cours de développement qui diminue après section de la moelle épinière. La diminution de l’expression du KCC2 dépolarise l’action du GABA et de la glycine, ce qui conduit donc à une réduction de l'efficacité de synapse inhibitrice. Le but de ce projet est d’explorer si chez l’Homme une section traumatique de la moelle épinière qui prive les neurones inhibiteurs de leur contrôle suprasegmentaire a pour conséquence de modifier leur comportement synaptique, voire de les ramener à un fonctionnement « immature », c’est-à-dire de transformer des synapses inhibitrices en synapses facilitatrices. Pour tester cette hypothèse, nous avons étudié l’effet sur des synapses inhibitrices de la moelle épinière d’une prise per os de furosémide, un antagoniste de KCC2, et comparé ses effets chez des sujets sains et chez des patients porteurs d’une section de la moelle épinière. L’étude sur les sujets sains suggère que le furosémide (40 mg) a pour effet une réduction du fonctionnement des synapses inhibitrices. Cet effet du furosémide sur les synapses inhibitrices semble être réduit chez des patients. Les résultats obtenus chez les sujets sains indiquent que furosémide administré per os à des dose largement utilisé en clinique humain modifie sélectivement le fonctionnement des synapses inhibitrices et permet donc de disposer d’un mesure non-invasive de fonctionnement intrinsèque de la synapse inhibitrice. Les résultats préliminaires obtenus chez les patients porteurs d’une section de la moelle épinière suggèrent une réduction de l’efficacité de synapses inhibitrices qui probablement contribue à la spasticité. La stimulation électrique transcrânienne de courant continu encore appelée « transcranial direct current stimulation (tDCS) » par les anglo-saxons, a connu un essor considérable et constitue aujourd’hui une technique de référence pour moduler l’excitabilité du cortex chez l’Homme. En 2009, Roche et al. ont montré dans notre laboratoire, que la tDCS anodale appliquée sur l’hémisphère contralateral pouvait également modifier l’excitabilité des réseaux neuronaux spinaux (i.e. l’inhibition réciproque au niveau du poignet) enregistrée sur le côté dominant chez les sujets sains. L’existence de projection corticale ipsilatérale sur les réseaux neuronaux spinaux de la moelle épinière et leurs éventuelles modifications après lésion cortico-sous-corticale reste très controversée. Dans ce projet, nous avons testé les effets de la tDCS ipsi- et contralarérale du cortex non-lésé sur l’inhibition réciproque chez des patients AVC. La tDCS ipsilatérale n’induit pas de modifications de l’inhibition réciproque chez les sujets sains. Des résultats similaires enregistrés sur le membre supérieur lésé ont été observés chez des patients AVC, mais ces résultats mériteraient d’être confortés avec un plus grand nombre de sujets. La tDCS contralatérale chez les sujets sains n’induit pas de modifications de l’inhibition réciproque enregistrées sur le membre supérieur non-dominant. Ce résultat est différent de celui observé sur le membre supérieur dominant par Roche et al. (2009). Ce contrôle asymétrique sur l'inhibition réciproque est argument en faveur de l'hypothèse que l'inhibition inter-hémisphérique (IHI) entre les deux cortex moteurs est asymétrique. L’IHI à partir de l'hémisphère «dominant» est probablement plus importante. / My thesis is devoted to the study of the spinal circuitry involved in motor functions using non-invasive electrophysiological methods in humans. It comprises two research projects.Studies in animals have shown that during neural development, GABAergic and glycinergic neurons are first excitatory, and then become inhibitory during maturation. This developmental transition is mainly due to the activation of co-transporter KCC2 at the mature state. A down-regulation of KCC2 was reported after spinal cord transection in the rat that leads to the depolarising (excitatory) action of GABA and glycine and thus results in a reduction of inhibitory synaptic efficiency. The aim of this project was to explore if spinal cord injury (SCI) in human reverses the pattern of GABAergic and glycinergic neurons back towards the immature state (primarily excitatory). To test this hypothesis, we studied the effects of furosemide (a KCC2 antagonist) on spinal inhibitory synaptic function, and compared the results obtained in healthy subjects and SCI patients. Results in healthy subjects suggest that furosemide (40 mg, orally-administrated) induces a reduction of inhibitory synapse functions. This effect of furosemide on inhibitory synapses seems to be reduced in SCI patients. Our results suggest that furosemide has the potential to test functions of inhibitory synapses in humans. The difference of furosemide effects on spinal inhibitory synapse excitability in healthy subjects and SCI patients favours the hypothesis of a decrease in inhibitory neuronal activity induced by down-regulation of KCC2 after SCI in humans that likely contributes to spasticity. Transcranial direct current stimulation (tDCS) has emerged as a method for exploring cortex excitability in humans. Roche et al. (2009) have shown in our laboratory that using anodal tDCS over contralateral motor cortex can also induce changes in spinal network excitability (i.e. reciprocal inhibition between forearm muscles) in the dominant limb in healthy subjects. It is unknown whether motor activity from the unaffected cerebral hemisphere could be employed after semi-brain damage in patients with hemiplegia. Moreover, little is known about the non-affected limb if it always functions like 'normal' after unilateral stroke. In this project, the ipsi- and contralateral corticospinal controls on reciprocal inhibition between forearm muscles were explored using anodal tDCS applied over the unaffected motor cortex of stroke patients and then compared to the results obtained in healthy subjects. Ipsilateral tDCS induces no change in reciprocal inhibition in healthy subjects. Similar results recorded on the affected upper limb are observed in stoke patients. However a larger number of patients is required to confirm the results. Contralateral anodal tDCS in healthy subjects shows no changes of reciprocal inhibition recorded in the non-dominant upper limb. This result is different from that observed in the dominant upper limb by Roche et al. (2009). This asymmetrical control on reciprocal inhibition would favour the hypothesis that the inter-hemispheric inhibition (IHI) between both motor cortices is asymmetric, with prominent IHI projections originating in the “dominant” left hemisphere. Contralateral anodal tDCS of the unaffected motor cortex induces a strong decrease in reciprocal inhibition in non-affected upper limb in stoke patients.This is different from that observed in both dominant and non-dominant upper limb in healthy subjects suggesting that the pathophysiological changes after unilateral stroke would probably not occur only on the hemiparesis side, but may also the non-affected side. A larger number of patients is still required to confirm the results.

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Vandetanib, lenvatinib and cabozantinib are inhibitors of receptor tyrosine kinases approved to treat locally advanced or metastatic thyroid gland, kidney and liver cancers. These multi- kinase inhibitors, inhibit phosphorylation of tyrosine moieties of protein, thus modulate cell signalization in cancer cells. Metabolites of vandetanib, lenvatinib and cabozantinib were detected in vitro as well as in vivo in blood and urine. Cytochromes P450 and flavin monooxygenases were identified as primary enzymes participating in metabolism of these drugs. Literature lacks information regarding pharmacological efficacy of vandetanib, lenvatinib and cabozantinib metabolites. The aim of this diploma thesis was the investigation of pharmacological efficacy of N-oxides of vandetanib, lenvatinib and cabozantinib. The viability measurement under normoxic and hypoxic conditions was employed to determined their efficacy. The expression of enzymes of the first phase of xenobiotics metabolism (CYP 450 1A1, 1B1, 3A4 a CYP 450 oxidoreductase) and receptor tyrosine kinases RET and VEGFR2, as well as mechanism of changes in their expression were investigated using western blotting and flow cytometry. High performance liquid chromatography was utilised to investigate possible metabolism of tyrosine kinase inhibitors and...

This master´s thesis deals with the analysis of experimental telemetrical ECG records with intention to determine the long-term influence of anticancer drug sunitinib on the electrical activity of heart. A laboratory rat was chosen as a model organism for the experimental study carried out at the Department of Physiology at Faculty of Medicine, Masaryk university. The sunitinib was applied to the rats at an early age and the ECG was measured with a 20-week delay using the Stellar telemetry system. To measure the effect of sunitinib on the electrical activity of the heart chambers, an analysis of the duration of the RR and QT interval and the width of the QRS complex was chosen. These parameters were detected by the wavelet transform method. Statistical analysis was performed using nonparametric tests - the Wilcoxon signed rank test, the MannWhitney test and the Friedman Test. The obtained results suggest that the use of sunitinib has no long-term effect on the observed parameters for the chosen animal model. After extension of the study, the results obtained could contribute to assess the effect of drugs on electrical activity of the human heart several decades after sunitinib treatment termination.

This diploma thesis is focused on proposition of non-freezing heat transfer fluid for solar systems. Fluid will be based on mixture of new available compound propane-1,3-diol with water and modern corrosion inhibitors. Then will be investigate, if this new compound is competetive to common used liquids like ethylene glycol or propylene glycol.